Late effects of prematurity: Psychiatric outcomes of 17-year-olds born very preterm.

AIM: Very preterm (VPT) birth is a known early vulnerability factor, impacting both physical and mental health over the life-span. The additional burden of psychiatric illness in VPT adolescents is likely to adversely affect critical developmental tasks and personal, social and academic/vocational trajectories. Our aim was to examine the magnitude and extent of the risk of psychological burden by determining the prevalence of psychiatric disorders in our prospectively followed-up VPT and full-term (FT) control cohorts, in this period of developmental transition at age 17 years. METHODS: Rates of psychiatric disorder in the VPT and FT control cohorts were ascertained at clinical interview of the adolescents and their care giver(s) by an adolescent psychiatrist. RESULTS: VPT birth was associated with a greater risk of generalised anxiety disorder (VPT vs. FT risk ratio (RR) 2.33; 95% confidence interval (CI): 1.16, 4.67, P = 0.02), as well as attentional problems (VPT vs. FT RR 3.46; 95% CI: 1.01, 11.88, P = 0.03). Although care givers of VPT adolescents reported many social and communication difficulties, and observation at clinical interview supported this, our data did not reach clinical threshold for group differences in autistic spectrum disorder. For all other psychiatric disorders, there was no difference between VPT and FT control adolescents. CONCLUSION: Our longitudinal cohort follow-up study examining the late effects of VPT birth has demonstrated increased rates of clinically significant psychiatric disorder in this period of important developmental transition. Families and health professionals need to be aware of the increased risk so they can monitor for symptoms and seek effective mental health treatments and support.

Systematic review: Accuracy of the enhanced liver fibrosis test for diagnosing advanced liver fibrosis and cirrhosis.

BACKGROUND AND AIMS: The rising incidence of chronic liver disease (CLD) has increased the need for early recognition. This systematic review assesses the diagnostic accuracy of the enhanced liver fibrosis (ELF) test in cases of advanced fibrosis and cirrhosis due to multiple etiologies in at-risk populations. METHODS: Studies evaluating the ELF accuracy in identifying advanced fibrosis or cirrhosis, defined as METAVIR stage F ≥ 3 and F = 4 or equivalent, in patients with non-alcoholic fatty liver disease (NAFLD), alcohol liver disease (ALD), or viral hepatitis were included. Liver biopsy was used as the reference standard. Medline and Embase databases were searched. The QUADAS-2 tool was used as a framework to assess risk of bias and applicability. The area under the receiver operator curve (AUROC) was extracted as a summary measure of diagnostic accuracy. RESULTS: Thirty-six studies were included: 11 hepatitis C, 4 hepatitis B, 9 NAFLD, 2 ALD, and 10 mixed. The ELF test showed good diagnostic performance in detecting advanced fibrosis in patients with viral hepatitis (AUROC 0.69 to 0.98) and excellent performance in NAFLD (AUROC 0.78 to 0.97) and ALD (AUROC from 0.92 to 0.94). There is also evidence of good diagnostic performance for detecting cirrhosis in patients with viral hepatitis (AUROC 0.63 to 0.99), good performance in NAFLD (AUROC 0.85 to 0.92), and excellent performance in patients with ALD (AUROC 0.93 to 0.94). CONCLUSION: This systematic review supports the use of the ELF test across a range of CLD as a possible alternative to liver biopsy in selected cases.

Influences on childhood immunisation decision-making in London's Gypsy and Traveller communities.

AIMS: Uptake of childhood immunisations is lower among Gypsy, Roma and Traveller (GRT) communities than in the general UK population. This small-scale study aimed to elicit insights from GRT mothers on their interaction with health services in London around childhood immunisations. The purpose was to inform a larger piece of work by the NHS England and Improvement (London) Public Health Commissioning Team to inform their planning to improve access to vaccination services for GRT communities in London. STUDY DESIGN: An exploratory qualitative study using semi-structured interviews and a focus group. METHODS: There was purposive sampling of mothers from any GRT background from south-west London using snowballing methods. One focus group and three interviews were conducted. A thematic analysis approach was used. RESULTS: A total of nine women were recruited and seven participated between March and April 2018. Five themes were identified: adherence with antenatal care, self-declared parenting expertise, family support, childhood immunisations, keep children healthy but 'they say wait on the MMR until they are talking'. CONCLUSION: Compliance with antenatal care, strong parenting beliefs and cohesive family support are strong influences on decision-making regarding immunisations. The women interviewed emphasised their own expertise in child rearing. This was occasionally at odds with the health advice provided by health professionals. The women widely shared their experiences of health professionals with other family and community members and this impacted on others' intention to vaccinate. These are key issues that should be considered when trying to improve uptake of immunisations in GRT families in a face-to-face manner. Equally, it warrants further exploration in a larger-scale study to see whether this reflects the wider community and in order to tailor supplementary immunisation activities to improve uptake.

Factors affecting N-terminal pro-B-type natriuretic peptide levels in preterm infants and use in determination of haemodynamic significance of patent ductus arteriosus.

This study aimed to investigate factors affecting N-terminal pro-B-type natriuretic peptide (NTproBNP) in preterm infants and the ability of NTproBNP to predict haemodynamically significant patent ductus arteriosus (HsPDA). Prospective cohort study of 51 infants < 30 weeks gestation. Blood NTproBNP and heart ultrasound were performed on day of life 3, 10, 28 and 36 weeks corrected age. NTproBNP levels analysed for prediction of HsPDA. The effect of gestational age, ventilation, hypoxia, bronchopulmonary dysplasia (BPD), creatinine and haemoglobin levels on NTproBNP levels were investigated. Infants with HsPDA had higher mean (SD) day 3 NTproBNP (1840 pmol/L (1058) versus 178 pmol/L (140) p < 0.001). Receiver operator curves of day 3 NTproBNP for prediction of day 3 and day 10 HsPDA had an area under the curve of 0.98 and 0.94, respectively. A chosen day 3 NTproBNP value of ≥ 287 pmol/L for the prediction of day 3 HsPDA correctly classified 92% (sensitivity 92%, specificity 92%). NTproBNP demonstrated only modest ability to predict severe BPD. Chronological but not gestational age affected NTproBNP. Ventilation, hypoxia and haemoglobin levels did not influence NTproBNP but creatinine level was positively correlated. CONCLUSION: Day 3 NTproBNP is a useful biomarker to predict HsPDA and may be a valuable tool in future trial design. What is Known: • NTproBNP is a cardiac hormone used to diagnose and monitor cardiac dysfunction in adults and has been shown to be higher in premature infants with haemodynamically significant ductus arteriosus (HsPDA). What is new: • NTproBNP is highly predictive of ultrasound-defined HsPDA and may be a useful tool for further triage • Early NTproBNP higher in infants who develop severe BPD and with renal impairment but not affected by gestational age, recent exposure to hypoxia or haemoglobin levels while late levels unexpectedly higher in those without BPD or HsPDA.

Combining remote sensing and on-site monitoring methods to investigate footpath erosion within a popular recreational heathland environment.

Footpaths are a prominent consequence of natural area tourism and reflect damage caused to valuable, sensitive habitats by people pressure. Degradation impacts on vegetation, wildlife, on and off-site soil movement and loss, creation of additional informal off-path footpaths (desire lines), and visual destruction of landscapes. Impacts need to be measured and monitored on a large temporal and spatial scale to aid in land management to maintain access and preserve natural environments. This study combined remote sensing (Light Detection and Ranging [LiDAR] and aerial photography) with on-site measurement of footpaths within a sensitive heathland habitat (Land's End, Cornwall, UK). Soil loss, slope angle change, vegetation damage and a hydrology model were combined to comprehensively study the site. Results showed 0.09 m mean soil loss over five years, footpath widening, increasing grass cover into heathland, and water channelling on the footpaths exacerbating erosion. The environments surrounding the footpaths were affected with visitors walking off path, requiring further management and monitoring. Multiple remote sensing techniques were highly successful in comprehensively assessing the area, particularly the hydrology model, demonstrating the potential of providing a valuable objective and quantitative monitoring and management tool.

Cardiac structure and function in very preterm-born adolescents compared to term-born controls: A longitudinal cohort study.

BACKGROUND: There is emerging evidence of differences in cardiac structure and function in preterm-born adults and increased risk of heart failure. However, there is a paucity of data in populations who have been exposed to modern intensive care and the impact of perinatal factors is unclear. AIMS: To compare echocardiographic measures of cardiac structure and function in a regional cohort of 17-year-olds born very preterm compared to term-born peers and the influence of perinatal factors. STUDY DESIGN: Observational longitudinal cohort study. SUBJECTS: A regional cohort of ninety-one 17-year-olds born at <32 weeks gestation compared to sixty-two term-born controls. OUTCOME MEASURES: Echocardiographic measures of cardiac structure and function. RESULTS: Left ventricular and right atrial volume and left ventricular mass, indexed to body surface area, were significantly smaller in preterm-born adolescents compared to term-born controls even when adjusted for sex. There were no between group differences in cardiac function. Within those born preterm we found a significant association between gestational age and birthweight z-score and measures of cardiac function at 17 years. Within the preterm group, those with a diagnosis of bronchopulmonary dysplasia had higher left ventricular posterior wall thickness, higher mitral deceleration time and lower left atrial area and tricuspid annular plane of systolic excursion. CONCLUSIONS: Adolescents born very prematurely, who have received modern intensive care, have measurable differences in heart structure compared to their term-born peers but heart function is preserved. For those born preterm, gestational age, birthweight and bronchopulmonary dysplasia are associated with differences in cardiac function.

Measuring the impact of a burns school reintegration programme on the time taken to return to school: A multi-disciplinary team intervention for children returning to school after a significant burn injury.

INTRODUCTION: Returning to school can be a major step for burn-injured children, their family, and staff and pupils at the receiving school. Previous literature has recognised the difficulties children may face after a significant injury and factors that may influence a successful reintegration. AIM: A regional paediatric burns service recognised that some patients were experiencing difficulties in returning to school. A baseline audit confirmed this and suggested factors that hindered or facilitated this process, initiating the development of a school reintegration programme (SRP). Since the programme's development in 2009, it has been audited annually. The aim of this paper was to evaluate the impact of the SRP by presenting data from the 2009 to 2011 audits. METHOD: For the baseline audit, the burn care team gathered information from clinical records (age, gender, total body surface area burned (TBSA), skin grafting and length of stay) and telephone interviews with parents and teachers of the school returners. For the re-audits, the same information was gathered from clinical records and feedback questionnaires. RESULTS: Since its introduction, the mean length of time from discharge to return to school has dropped annually for those that opted into the programme, when compared to the baseline by 62.3% (53 days to 20 days). Thematic analysis highlights positive responses to the programme from all involved. Increased awareness and feeling supported were amongst the main themes to emerge. CONCLUSIONS: Returning to school after a significant burn injury can be challenging for all involved, but we hypothesise that outreach interventions in schools by burns services can have a positive impact on the time it takes children to successfully reintegrate.

Oncogenic B-RAF signaling in melanoma impairs the therapeutic advantage of autophagy inhibition.

PURPOSE: Metastatic melanoma is characterized by extremely poor survival rates and hence novel therapies are urgently required. The ability of many anticancer drugs to activate autophagy, a lysosomal-mediated catabolic process which usually promotes cell survival, suggests targeting the autophagy pathway may be a novel means to augment therapy. EXPERIMENTAL DESIGN: Autophagy and apoptosis were assessed in vitro in human melanoma cell lines in response to clinically achievable concentrations of the endoplasmic reticulum (ER) stress-inducing drugs fenretinide or bortezomib, and in vivo using a s.c. xenograft model. RESULTS: Autophagy was activated in response to fenretinide or bortezomib in B-RAF wild-type cells, shown by increased conversion of LC3 to the autophagic vesicle-associated form (LC3-II) and redistribution to autophagosomes and autolysosomes, increased acidic vesicular organelle formation and autophagic vacuolization. In contrast, autophagy was significantly reduced in B-RAF-mutated melanoma cells, an effect attributed partly to oncogenic B-RAF. Rapamycin treatment was unable to stimulate LC3-II accumulation or redistribution in the presence of mutated B-RAF, indicative of de-regulated mTORC1-dependent autophagy. Knockdown of Beclin-1 or ATG7 sensitized B-RAF wild-type cells to fenretinide- or bortezomib-induced cell death, demonstrating a pro-survival function of autophagy. In addition, autophagy was partially reactivated in B-RAF-mutated cells treated with the BH3 mimetic ABT737 in combination with fenretinide or bortezomib, suggesting autophagy resistance is partly mediated by abrogated Beclin-1 function. CONCLUSIONS: Our findings suggest inhibition of autophagy in combination with ER stress-inducing agents may represent a means by which to harness autophagy for the therapeutic benefit of B-RAF wild-type melanoma.